Disorders associated with abnormalities in storage and release of histamine were investigated by sensitive isotopic and enzymatic assay procedures. Histamine was identified as the causative agent of hyperhistaminemia in a variety of disorders. These included patients with cold- and exercise-induced urticaria, Philadephia chromosome chronic granulocytic leukemia and a patient with gastric carcinoma. Treatment with the H2 blocker metiamide resulted in remission of symptoms.